Optical effects of anti-TGFbeta treatment after photorefractive keratectomy in a cat model.
OBJECTIVE
To assess the contribution of corneal myofibroblasts to optical changes induced by photorefractive keratectomy (PRK) in a cat model.


METHODS
The transforming growth factor (TGF)-beta-dependence of feline corneal keratocyte differentiation into alpha-smooth muscle actin (alphaSMA)-positive myofibroblasts was first tested in vitro. Twenty-nine eyes of 16 cats were then treated with -10 D PRK in vivo and divided into two postoperative treatment groups that received either 100 microg anti-TGFbeta antibody for 7 days, followed by 50 microg dexamethasone for another 7 days to inhibit myofibroblast differentiation, or vehicle solution for 14 days (control eyes). Corneal thickness and reflectivity were measured by optical coherence tomography. Wavefront sensing was performed in the awake-behaving state before surgery and 2, 4, 8, and 12 weeks after surgery. Wound healing was monitored using in vivo confocal imaging and postmortem alphaSMA immunohistochemistry.


RESULTS
In culture, TGFbeta caused cat corneal keratocytes to differentiate into alphaSMA-positive myofibroblasts, an effect that was blocked by coincubation with anti-TGFbeta antibody. In vivo, anti-TGFbeta treatment after PRK resulted in less alphaSMA immunoreactivity in the subablation stroma, lower corneal reflectivity, less stromal regrowth, and lower nonspherical higher order aberration induction than in control eyes. However, there were no intergroup differences in epithelial regeneration or lower order aberration changes.


CONCLUSIONS
Anti-TGFbeta treatment reduced feline corneal myofibroblast differentiation in vitro and after PRK. It also decreased corneal haze and fine-grained irregularities in ocular wavefront after PRK, suggesting that attenuation of the differentiation of keratocytes into myofibroblast can significantly enhance optical quality after refractive surface ablations.
Bühren
Jens
J
University of Rochester Eye Institute, University of Rochester, Rochester, New York 14642, USA.
Nagy
Lana
L
Swanton
Jennifer N
JN
Kenner
Shawn
S
MacRae
Scott
S
Phipps
Richard P
RP
Huxlin
Krystel R
KR
D000199:Actins / Q000378:metabolism; D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology*; D015153:Blotting, Western; D002415:Cats; D018929:Cell Culture Techniques; D002454:Cell Differentiation / Q000187:drug effects; D003315:Cornea / Q000378:metabolism / Q000473:pathology* / Q000601:surgery*; D019781:Corneal Topography; D003907:Dexamethasone / Q000494:pharmacology; D005347:Fibroblasts / Q000378:metabolism / Q000473:pathology; D019084:Fluorescent Antibody Technique, Indirect; D005938:Glucocorticoids / Q000494:pharmacology; D054018:Lasers, Excimer / Q000627:therapeutic use*; D018613:Microscopy, Confocal; D023421:Models, Animal; D018903:Photorefractive Keratectomy / Q000379:methods*; D041623:Tomography, Optical Coherence; D016212:Transforming Growth Factor beta / Q000276:immunology* / Q000494:pharmacology; D014945:Wound Healing / Q000187:drug effects / Q000502:physiology
D000199:Actins; D000911:Antibodies, Monoclonal; D005938:Glucocorticoids; D016212:Transforming Growth Factor beta; D003907:Dexamethasone